A5058991969- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- PARP inhibition in cancer therapy
- Renal cell carcinoma treatment
- Sarcoma Diagnosis and Treatment
- Colorectal Cancer Treatments and Studies
- Renal and related cancers
- Prostate Cancer Treatment and Research
- RNA Research and Splicing
- Cancer therapeutics and mechanisms
- RNA Interference and Gene Delivery
- CAR-T cell therapy research
- Thyroid Cancer Diagnosis and Treatment
- Tumors and Oncological Cases
- Renal Diseases and Glomerulopathies
- Ferroptosis and cancer prognosis
- Cancer Cells and Metastasis
- DNA Repair Mechanisms
- Single-cell and spatial transcriptomics
- Ovarian cancer diagnosis and treatment
- Immunotherapy and Immune Responses
- Ubiquitin and proteasome pathways
- Microtubule and mitosis dynamics
- Neuroblastoma Research and Treatments
- BRCA gene mutations in cancer
Harvard University
2020-2024
Dana-Farber Cancer Institute
2020-2024
Broad Institute
2022-2024
Massachusetts Institute of Technology
2024
Children's Cancer Therapy Development Institute
2016-2023
USC Norris Comprehensive Cancer Center
2016
Translocation renal cell carcinoma (tRCC) is a poorly characterized subtype of kidney cancer driven by MiT/TFE gene fusions. Here, we define the landmarks tRCC through an integrative analysis 152 patients with identified across genomic, clinical trial, and retrospective cohorts. Most tRCCs harbor few somatic alterations apart from fusions homozygous deletions at chromosome 9p21.3 (19.2% cases). Transcriptionally, display heightened NRF2-driven antioxidant response that associated resistance...
ABSTRACT PURPOSE Identification of discrete sub-groups associated with treatment response and resistance in localized Ewing sarcoma (EWS) remains a challenge. The primary objective the Children’s Oncology Group biology study AEWS18B1-Q was to perform molecular characterization large cohort patients treated on prospective trials modern standard care therapy. METHODS We analyzed clinical features from EWS enrolled AEWS0031, AEWS1031, or INT-0154 frontline trials. All had available FFPE tissue,...
Previous germline studies on renal cell carcinoma (RCC) have usually pooled clear and non–clear RCCs not adequately accounted for population stratification, which might led to an inaccurate estimation of genetic risk. Here, we aim analyze the major drivers RCC risk clinically relevant but underexplored variant types. We first characterized pathogenic variants (PVs), cryptic splice variants, copy number (CNVs) in 1436 unselected patients. To evaluate enrichment PVs RCC, conducted a...
Relapsed and metastatic hepatoblastoma represents an unmet clinical need with limited chemotherapy treatment options. In a chemical screen, we identified volasertib as agent in vitro activity, inhibiting cell growth while sparing normal hepatocytes. Volasertib targets PLK1 prevents the progression of mitosis, resulting eventual death. is overexpressed biopsies relative to liver tissue. As potential therapeutic strategy, tested combination relapse-related chemotherapeutic irinotecan. We found...
CIC -rearranged sarcomas (CRSs) have recently been characterized as a distinct sarcoma subgroup with less favorable prognosis compared to other small round cell sarcomas. CRSs share morphologic features Ewing's and prior 2013 were grouped under undifferentiated phenotype by the WHO classification. In this report, whole-genome sequencing RNA performed for an adolescent male patient CRS who was diagnosed pleomorphic (UPS) three contemporary institutions. Somatic mutation analysis identified...
While immune-checkpoint blockade (ICB) has revolutionized treatment of metastatic melanoma over the last decade, identification broadly applicable robust biomarkers been challenging, driven in large part by heterogeneity ICB regimens and patient tumor characteristics. To disentangle these features, we performed a standardized meta-analysis eight cohorts patients treated with anti-PD-1 (n=290), anti-CTLA-4 (n=175), combination anti-PD-1/anti-CTLA-4 (n=51) RNA sequencing pre-treatment clinical...
The introduction of immune checkpoint blockade (ICB) has markedly improved outcomes for advanced melanoma. However, many patients develop resistance through unknown mechanisms. While combination ICB response rate and progression-free survival, it substantially increases toxicity. Biomarkers to distinguish who would benefit from therapy versus aPD-1 remain elusive. We analyzed whole-exome sequencing pretreatment tumors four cohorts ( n = 140) ICB-naïve treated with aPD-1. High genomic...
Rhabdomyosarcoma (RMS) is the most common childhood soft-tissue sarcoma. The largest subtype of RMS embryonal rhabdomyosarcoma (ERMS) and accounts for 53% all RMS. ERMS typically occurs in head neck region, bladder, or reproductive organs portends a promising prognosis when localized; however, metastatic 5-yr overall survival rate ∼43%. genomic landscape demonstrates range putative driver mutations, thus recognition pathological mechanisms driving tumor maintenance should be critical...
Abstract While the introduction of immune checkpoint blockade (ICB) has dramatically improved clinical outcomes for patients with advanced melanoma, a significant proportion develop resistance to therapy, and mechanisms are poorly elucidated in most cases. Further, while combination ICB higher response rates progression free survival compared single agent therapy front line setting, there is significantly increased toxicity ICB, biomarkers identify who would disproportionately benefit from...
Abstract Background: Clear cell renal carcinoma (ccRCC) is characterized by mutations in epigenetic modulators and aberrant transposable element (TE) expression, each of which have been separately associated with immunotherapy (IO) benefit specific clinical contexts. However, the relationship between regulators TE potential effect both somatic expression on outcomes, has not fully investigated. Methods: We utilized RNA sequencing from ccRCC patients’ tumors lines to quantify subfamily...
Abstract Background: Despite significant advances, only a subset of patients with advanced melanoma treated immune checkpoint blockade (ICB) experience durable responses, and biomarkers to predict response are limited. Further, while combination ICB has higher rates improved progression-free survival compared single-agent therapy in the front-line setting, there is significantly increased toxicity ICB, identify who would disproportionately benefit from vs aPD-1 poorly characterized. Methods:...
Rhabdomyosarcoma (RMS) is a mesenchymal malignancy phenocopying muscle and among the leading causes of death from childhood cancer. Metastatic alveolar rhabdomyosarcoma most aggressive subtype with an 8% 5-yr disease-free survival rate when chromosomal fusion present 29% negative for event. The underlying biology PAX -fusion-negative remains largely unexplored exceedingly rare in Li–Fraumeni syndrome patients. Here, we case 11-yr-old male fusion-negative studied at end life comprehensive...
ABSTRACT Translocation renal cell carcinoma (tRCC) is an aggressive and poorly-characterized subtype of kidney cancer driven by MiT/TFE gene fusions. Here, we define the landmarks tRCC through integrative analysis 152 patients identified across multiple genomic, clinical trial, retrospective cohorts. Most tRCCs harbor few somatic alterations apart from fusions homozygous deletions at chromosome 9p21.3 (19.2% cases). Transcriptionally, display a heightened NRF2-driven antioxidant response...
Abstract Alveolar and embryonal rhabdomyosarcoma (RMS) are soft-tissue cancers that affect children, adolescents, young adults. Sometimes referred to as muscle cancer, RMS is a cancer of non-muscle origin phenocopies incompletely differentiated myoblasts or activated satellite (muscle stem) cells. Interestingly, (ERMS) has been observed undergo terminal myogenic differentiation in response stress induced by chemotherapy radiation therapy 4, 9, 24 . Given the propensity differentiation, this...
ABSTRACT IMPORTANCE RCC encompasses a set of histologically distinct cancers with high estimated genetic heritability, which only portion is currently explained. Previous rare germline variant studies in have usually pooled clear and non-clear cell RCCs not adequately accounted for population stratification that may significantly impact the interpretation discovery certain candidate risk genes. OBJECTIVE To evaluate enrichment PVs established cancer-predisposing genes (CPGs) patients...
<div>Abstract<p>Alterations in DNA damage response (DDR) genes are common advanced prostate tumors and associated with unique genomic clinical features. ATM is a DDR kinase that has central role coordinating repair cell-cycle following damage, <i>ATM</i> alterations present approximately 5% of tumors. Recently, inhibitors PARP have demonstrated activity harboring gene alterations, particularly <i>BRCA1/2</i> alterations. However, the beyond mediating...
<p>Immunofluorescence and IR survival data; additional methods</p>
<p>Immunofluorescence and IR survival data; additional methods</p>